ACR Boston 2014 | Daily Highlights

The Efficacy and Safety of Tocilizumab Subcutaneous Q2W and Following Escalation from Q2W to QW Therapy in Combination with Traditional Dmards in Patients with Moderate to Severe Rheumatoid Arthritis at 96 Weeks

Background:
The BREVACTA study assessed the efficacy and safety of subcutaneous tocilizumab (TCZ SC) in patients (pts) with RA who had an inadequate response to ≥ 1 DMARD (21% previously failed aTNF therapy). The primary objective assessed efficacy and safety to Week 24. Superiority over placebo (PBO) was observed, with a safety profile comparable to intravenous (IV) TCZ. We now report the efficacy and safety data for TCZ SC every 2 weeks (q2w) and TCZ weekly (qw) following escalation from either TCZ q2w or PBO q2w to Week 96.

Methods:
This phase 3, randomized, multicenter, parallel arm study included a 24 week double blind, PBO controlled period followed by a 72 week open label phase and a further 8 weeks of safety follow up. Pts were initially randomized 2:1 to receive TCZ SC 162 mg q2w (n=437) or PBO SC q2w (n=219) via prefilled syringe (PFS) with prestudy DMARD(s). At Week 24, pts in both arms were rerandomized 1:1 to receive open label TCZ SC q2w via PFS or autoinjector pen. These data focus on pts who were rerandomised at Week 24 and received TCZ SC regardless of injection device. Escape therapy with TCZ SC qw was available for pts with an inadequate efficacy response from Week 12. At the first dose on escape therapy pts were rebaselined; efficacy is from time of escape up to Week 84 and safety is from time of escape to the end of the study.

Results:
In the open label phase, 338 pts (77%) were maintained on TCZ SC q2w and 119 (54%) switched from the PBO to TCZ SC q2w. For the escape pts, in the double blind phase, 72 (16.5%) escaped from the TCZ arm and 90 (41.3%) from the PBO arm, while in the open label phase 27 (5.9%) escaped from the TCZ SC q2w arm. In the TCZ q2w arm, the proportion of pts who achieved ACR20/50/70 responses increased up to Week 96. In the TCZ q2w arm, the rates of AEs and SAEs, including serious infections, remained stable or decreased up to Week 96. No anaphylaxis or serious hypersensitivity occurred. By Week 96, 31 pts (7.1%) withdrew due to AEs and 7 pts (1.6%) died. Nine pts (2.1%) developed antiTCZ antibodies postbaseline without loss of efficacy or clinically significant hypersensitivity. For escape pts, the proportion of pts who achieved an ACR20 response increased after escape in both the TCZ or PBO arms; although there was a higher ACR20 response in escape pts from the PBO arm than the TCZ q2w arm (86.4% and 63%, respectively) at Week 84. The rate of AEs per 100 pt years, following escape therapy was similar between pts who previously received TCZ or PBO (331.9 and 360.5, respectively) and comparable to the TCZ q2w arm (332.8).

Conclusions:
TCZ SC q2w demonstrated long term efficacy, including sustained ACR responses over 96 weeks. The AE profile for TCZ SC at 96 weeks was comparable to 24 weeks. For escape pts, there were improvements in ACR20 response rates in pts who previously received PBO and escalated from q2w to qw. TCZ SC will offer an alternative route of administration and the possibility of self administration for pts with RA.